Carboxymethyloxysuccinic anhydrides, halides and derivatives thereof

ABSTRACT

Carboxymethyloxysuccinic anhydrides and/or halides, their reaction products with active hydrogen compounds and methods for preparing the anhydrides, the halides and the reaction products are disclosed. The reaction products are variously useful in the fields of food flavorings, detergent builders, surfactants, lubricants, coatings, sizing agents and gasoline additives.

This application is a divisional of Ser. No. 797,226, filed May 16,1977, now U.S. Pat. No. 4,093,634.

BACKGROUND OF THE INVENTION

Carboxymethyloxysuccinic acid, hereinafter referred to as CMOSA, is aknown, highly biodegradable ether tricarboxylic acid which isconveniently prepared from maleic anhydride and glycolic acid asdescribed in U.S. Pat. No. 3,914,297 incorporated herein by reference.CMOSA is unique compared to the most similar, structurally analogousether polycarboxylic acid, namely, oxydiacetic acid. Thus, CMOSA is arelatively safe substance having known utility as a food acidulant andflavoring material (see U.S. Pat. No. 4,015,023) whereas oxydiaceticacid is a known toxic substance. Accordingly, introduction of acarboxymethyloxysuccinic acid residue into an organic molecule to obtainuseful polyfunctionality while at the same time not impairing thebiodegradability or safety characteristics of the molecule has become adesirable objective.

It is therefore an object of this invention to provide methods forpreparing the anhydrides and acid halides of carboxymethyloxysuccinicacid.

It is also an object of this invention to provide useful novelderivatives of the anhydrides and acid halides ofcarboxymethyloxysuccinic acid.

These and other objects will become apparent as the descriptionproceeds.

The attainment of the above objects is made possible by the conversionof CMOSA into novel anhydrides and/or acid halides. The anhydride andacid halide products are reacted with selected active hydrogen compoundssuch as water, hydrogen sulfide, ammonia, amines, alcohols, polyols,carbohydrates, amino acids and the like to produce a variety of usefulderivatives of carboxymethyloxysuccinic acid.

DETAILED DESCRIPTION OF THE INVENTION I. Preparation of anhydrides andacid halides

Carboxymethyloxysuccinic acid is converted into anhydride species byreaction with either: (1) excess acetyl chloride either alone or in thepresence of pyridine or (2) excess acetic anhydride. These methodsafford mainly a mixture of anhydride species containing five- andsix-membered rings as well as polymeric species. This mixture may berepresented by the general structural formulae as follows: ##STR1## Morespecifically this mixture contains predominantly: ##STR2## The abovemixture of CMOS anhydride species will be subsequently referred to asFormula I.

A predominantly mono anhydride species of carboxymethyloxysuccinic acidcan be prepared by dehydration of CMOSA by the following methods: (1)heating CMOSA in a vacuum, (2) subjecting CMOSA to azeotropicdistillation with a suitable solvent such as 1,1,2,3-tetrachloroethaneor xylene and (3) reaction of one mole of acetyl chloride or thionylchloride per mole of carboxymethyloxysuccinic acid in a suitable solventsuch as dioxane, ether or tetrahydrofuran. The structure of this speciesis predominantly the five-membered ring species, ##STR3## and will bereferred to henceforth as Formula II.

In many instances the Formula II anhydride is preferred for preparingderivatives since there is only one anhydride ring per molecule. In thisway reaction with an active hydrogen compound introduces only one moleof the active hydrogen compound per mole of the Formula II anhydride.

A mixed anhydride chloride species, hereinafter designated as FormulaIII, is obtainable by reaction of at least two moles of a thionyl halideper mole of carboxymethyloxysuccinic acid. The product of this reactioncontains predominantly the following chemical species: ##STR4## whereinA is Cl, Br or I and preferably Cl.

By reaction with excess thionyl halides or phosphorus tri- orpenta-halides in the presence of zinc halides, the compounds of FormulaI, II or III can be converted into carboxymethyloxysuccinic trihalidesof the formula: ##STR5## wherein A is Cl, Br or I and preferably Cl.

The reactions utilized in the above preparations of the species ofFormulas I and IV are applications of known methods or combinations ofknown methods for preparing organic acid anhydrides and acid chlorides.Examples of such methods are those described in the text entitled"Synthetic Organic Chemistry" by R. B. Wagner and H. D. Zook, John Wiley& Sons, 1953, pp. 546-549 (especially section numbers 335, 337 and 338)and pp. 558-559 (especially section numbers 341 and 343) and thereferences cited therein (all of which are incorporated herein byreference). Specific illustrative preparations of the anhydride and/oracid halide species of carboxymethyloxysuccinic acid will be found inthe Examples of this specification.

The species of Formulas I, II, III and IV may also be reacted withvarious active hydrogen compounds to produce useful derivatives. Thespecies of Formulas III and IV are chemically more reactive than thoseof Formulas I and II. Also, the Formula III species produces the samederivatives as those of Formula I. Accordingly, in the description thatfollows it will be understood that whenever reactions of Formula I aredescribed, the same reactions apply to Formula III. Formula IV speciesis unique compared to the other species in that reactions with activehydrogen compounds leads to trisubstitution (e.g. reaction of Formula IVspecies with methanol giving rise to trimethylcarboxymethyloxysuccinate).

A non-limiting list of active hydrogen compounds which are useful forreaction with species of Formulas I, II, III and IV is as follows:water; hydrogen sulfide; hydroxyl compounds such as straight or branchedaliphatic alcohols containing one to twenty-four carbon atoms asexemplified by methanol, ethanol, isopropanol, butanol, octanol,dodecanol and the like; alicyclic alcohols such as cyclopentanol andcyclohexanol; phenol and substituted phenols such as cresol, anisole,the halo phenols and the like; polyols such as ethylene glycol,propylene glycol, 1,2-dihydroxybutane, 1,3-dihydroxybutane,1,4-dihydroxybutane, glycerol, pentaerythritol, sorbitol, mannitol,inositol and the like; carbohydrates such as glucose, sucrose, starch,cellulose, dextrins and the like; ammonia and amines such as thestraight or branched alkylamines containing one to about twenty twocarbon atoms as exemplified by methyl amine, ethyl amine, butyl amine,dodecyl amine and the like; alkylolamines such as monoethanolamine,diethanolamine, isopropanol amine, 2-hydroxybutyl amine and the like;hydrazine and alkane diamines wherein the alkane group contains 1 to 12carbons such as ethylene diamine, propane-1,3-diamine,butane-1,4-diamine, hexane-1,6-diamine and the like; amino acids such asglycine, sarcosine, α- and β-alanine, glutamic acid and the like andesters thereof; the thiol analogs of the foregoing such as the straightor branched alkyl mercaptans containing 1 to 12 carbon atoms asexemplified by methyl mercaptan, butyl mercaptan, dodecyl mercaptan andthe like; 2-mercaptoethanol, 1,2-dimercaptoethane, α- and β-thioglycerolthiophenol and the like.

More specific and preferred examples are as follows.

A. Reaction of the species of Formulas I, II, III or IV with wateryields the starting CMOSA and thus represents a method of purifyingcrude preparations of CMOSA especially when the anhydride and/or acidchloride has been subjected to a purification step prior to reactionwith water. Thus, the species of Formula I may be precipitated out of anorganic solvent such as methylene chloride/acetone at about -70° C. toyield a purified product which is then heated with excess water.Purified carboxymethyloxysuccinic acid may then be separated from theresulting solution by known methods such as evaporation in vacuo attemperatures below about 100° C.

B. Reaction of the species of Formulas I, II, III and IV with hydrogensulfide and/or an alkali metal hydrosulfide or a tertiary aminehydrosulfide produces thiolcarboxymethyloxysuccinic acids of thefollowing general structure (Formula V) ##STR6## wherein X₁, X₂ and X₃is OH or SH and at least one of X₁, X₂ and X₃ is SH. These compounds areuseful as foodstuff flavoring compounds and as metal ion sequestrants.In the form of the alkali metal, ammonium and alkylolammonium salts, thecompounds or the hydrated forms thereof, are useful as both metal ionsequestrants and detergents builders.

It will be understood that thiolcarboxymethyloxysuccinic acids preparedfrom the species of Formulas I and III will be a mixture ofthiolcarboxymethyloxysuccinic acids containing predominantly thefollowing structures (Formula VI) ##STR7##

Thiolcarboxymethyloxysuccinic acids prepared from the species of FormulaII will contain predominantly the following structures (Formula VII):##STR8## Further, thiolcarboxymethyloxysuccinic acid prepared from thespecies of Formula IV will be the single trithiol species (FormulaVIII): ##STR9##

The various thiolcarboxymethyloxysuccinic acids described above (i.e.,Formulas VI, VII and VIII) are obtainable by applying the known methodsfor converting acetic anhydride or mixed anhydrides into thiol acids.Thus, the methods of U.S. Pat. No. 2,412,036 and of Cronyn, et al,J.A.C.S. 74 4726 (1956), both of which are incorporated herein byreference are applicable. In applying the Cronyn, et al procedure,dioxane may be substituted for methylene chloride in order to increasethe solubility of the CMOSA anhydride or chloride species in thereaction medium. The crude thiolcarboxymethyloxysuccinic acid reactionproducts obtained by these methods are purified by first evaporating anyorganic solvent present, dissolving the remaining residue in water andpassing the resulting aqueous solution through a column of cationexchange resin. Evaporation of the eluate in vacuo leaves the purifiedthiolcarboxymethyloxysuccinic acid(s) as a residue or, if desired, theevaporation can be interrupted to provide a concentrated aqueoussolution (e.g. containing ca. 40-50% thiolcarboxymethyloxysuccinicacid(s)).

The following species (Formula IX) of thiolcarboxymethyloxysuccinicacid, ##STR10## is not present to any significant extent in any of theabove preparations of thiolcarboxymethyloxysuccinic acids (i.e. FormulasVI, VII and VIII). It is entirely possible, however, that this species,(i.e. Formula IX) may be made from thiolglycolic acid ##STR11## andmaleic acid using the teachings of U.S. Pat. No. 3,914,297 whichdescribe the preparation of CMOSA.

C. Reaction of the species of Formulas I, II or III with ammonia or aprimary or secondary alkyl amine produces amido ether polycarboxylatesalts or mixtures of their salts having the following general formula:##STR12## wherein Y is independently NH₂, NRR' or OM and at least one Yis always OM; wherein R is an alkyl group containing 6 to 22 carbonatoms or an alkylol group R₂ OH, wherein R₂ contains two to four carbonatoms; wherein R' is either H or R as defined above and wherein M isammonium or a RR'⁺ NH₂ cation.

The reaction is readily carried out using an aqueous solution of theamine in those cases where the amines are soluble in water and attemperatures ranging from room temperature to about 50° C. In thosecases where the amines are insoluble in water or are liquid at or aboveroom temperature, an excess of the amine is utilized as the reactionsolvent or an inert solvent such as diethyl ether, dibutyl ether andtetrahydrofuran is utilized. The Formulas I, II or III species are addedto the amine or solution of amine. Preferably, about six moles of amineare utilized per mole of Formula I species; three moles of amine, permole of Formula II species and four moles of amine, per mole of FormulaIII species. Reaction conditions from room temperature to the boilingpoint of the solvent utilized or to about 100° C. are sufficient for thereaction. The reaction mixture is initially cooled during the slowaddition of the species of Formulas I, II or III because of theexothermic nature of the reaction.

When Formula I or III species are utilized, the product will be amixture of mono- and di-substituted amide derivatives ofcarboxymethyloxysuccinic acid (i.e. one or two of the Y substituents ofFormula X is NRR').

When the Formula II species is utilized, the product will contain onlyone amide group per molecule (i.e. one Y substituent in Formula X isNRR').

In all cases the reaction products may be treated with an alkali metalhydroxide or carbonate to release the amine combined with carboxylgroups or hydrogen halide as salts, thereby producing compoundscontaining both amido functions and alkali metal carboxylate functions.The products are then purified by trituration with a suitable solventsuch as ether, acetone or alcohol and filtration, thereby removing theliberated amine. Addition purification may be readily accomplished byacidification of the product with aqueous mineral acid and filtration torecover the acid forms of the desired products where M in Formula X isH. The acid forms are then washed with water and neutralized with anaqueous alkali metal hydroxide, ammonia or with a substituted ammoniumcompound such as monoethanolamine, diethanclamine, triethanolamine,isopropanolamine, diisopropanolamine, triisopropanolamine or morpholineto produce useful surface active agents having the following generalstructure: ##STR13## wherein Y is independently NH₂, --NRR' or OM₁, andat least one Y is always OM₁ ; wherein R is an alkyl group containing 6to 22 carbon atoms or an alkyl group R₂ OH wherein R₂ contains two tofour carbon atoms; and wherein R' is H or R as defined above and whereinM₁ is H, an alkali metal, ammonium or a substituted ammonium cationselected from the group consisting of monoethanolammonium,diethanolammonium, triethanolammonium, isopropanolammonium,diisopropanolammonium, triisopropanolammonium and morpholinium cations.

For example, the following predominant amido ether carboxylate products,Formula XI, are obtained by starting with the Formula III species in theabove reaction and purification sequence. ##STR14## wherein M₁, R and R'are as defined above.

When Formula I species is utilized in the above reaction andpurification sequence, the product is a complex mixture containing notonly the species of Formula XI but additional species such as ##STR15##wherein M₁, R and R' have the same meanings as defined above.

In the case where Formula II species is utilized in the above reactionand purification sequence, the product is predominantly a mixture of thefirst two structures shown in Formula XI above.

The preferred amido ether carboxylate compounds for detergent propertiesare those in which R is selected from the group C₁₀ to about C₂₂ alkylchains (primary or secondary) and R' is H or an alkyl group containingone to about 6 carbon atoms and M₁ is a sodium or potassium cation. Thepreferred groups for wetting action are those compounds in which Rcontains C₅ to about C₉ alkyl chains (primary or secondary), R' is H orequal to R and M₁ is a sodium or potassium cation.

The aforesaid amido ether carboxylates are useful not only in detergentcompositions for washing fabrics and hard surfaces but also in personalcleaning compositions such as toilet bars, shampoos, hair rinses, skincleansing compositions and dentifrice products.

When the formula IV species is reacted with ammonia or with alkyl aminesusing the reaction conditions described above for reactions of FormulasI, II and III species with the same active hydrogen compounds and usingat least six moles of ammonia or amine per mole of Formula IV species,there is obtained the triamide or trisubstituted amides ofcarboxymethyloxysuccinic acid: ##STR16## wherein R₃, R₄ and R₅, whichmay be the same or different are selected from the group consisting ofhydrogen, a straight or branched chain hydrocarbon radical having from 1to 18 carbon atoms and an alkylol group R₆ OH wherein R₆ contains two tofour carbon atoms. Such compounds have utility in the fields oflubricants and textile sizing as disclosed in U.S. Pat. No. 3,959,373assigned to the instant assignee.

The compounds of Formula XIII are readily isolated and purified usingthe purification technique described above for isolating the amido ethercarboxylic acid compounds (Formula X, M═H) free of ammonia or aminereactant and finally purifying the product according to methodsdescribed in U.S. Pat. No. 3,959,373 (incorporated herein by reference).

D. In an additional embodiment of the invention, the Formula I, II andIII species are reacted with hydroxyl containing compounds to producepartial esters or carboxymethyloxysuccinic acid: ##STR17## wherein R₇,R₈ and R₉ represent hydrogen or hydrocarbyl radicals containing 1 to 24carbon atoms and at least one of the R₇, R₈ and R₉ groups is hydrogen.Some non-limiting representative examples of hydrocarbyl radicals arealkyl, cycloalkyl, alkenyl, aralkyl, alkaryl and aryl groups.

A preferred group of the hydroxyl containing compounds which may beutilized are the alkanols containing 1 to 20 carbon atoms. The resultingpartial esters of carboxymethyloxysuccinic acid (Formula XIV) are usefulas additives in non-leaded gasoline as described in U.S. Pat. No.3,926,580 which is incorporated herein by reference.

The partial esters may be completely esterified by conventionaltechniques to produce the tri-hydrocarbyl esters ofcarboxymethyloxysuccinic acid. These materials have known utility asdetergent solvents and plasticizers (U.S. Pat. No. 3,943,165).

When Formula IV species are reacted with the alkanols containing 1 to 20carbon atoms the tri-hydrocarbyl esters of carboxymethyloxysuccinic acidare obtainable directly. These derivatives are also useful in non-leadedgasoline as described in U.S. Pat. No. 3,926,580.

Other hydroxy compounds which may be reacted with Formula I, II, III andIV species to produce useful derivatives are: polyols such as ethyleneglycol, propylene glycol, glycerol, pentaerythritol and sorbitol;carbohydrates such as glucose, sucrose, starch, cellulose andoligosaccharides such as dextrins and hydrolyzed forms of starch andcellulose. The reaction products with the polymeric carbohydrates (e.g.starch) are useful for producing edible films, coatings, adhesives anddetergent builders.

E. Similarly, Formula I, III and IV species may be reacted withpolyamines such as ethylene diamine and propylene diamine to producepolymeric materials having useful properties for use in coatings,adhesives and humectant systems.

Having thus described the invention and its several and preferredembodiments, the following are detailed examples of the invention.

In the Examples below the structures of the products were confirmed byNMR (Varian T60 instrument) and/or infrared (Beckman IR-5A). All partsand percentages are by weight unless otherwise specified.

EXAMPLE 1 Preparation of Mixed CarboxymethyloxysuccinicAnhydrides--Formula I

One hundred grams (0.29 mole) of trisodium carboxymethyloxysuccinatepentahydrate is placed in a flask and acidified with 90 mls of 37%hydrochloric acid while stirring and cooling the mixture in an ice bath.The reaction mixture is then evaporated to dryness in vacuo. Theevaporation residue is then taken up in about 150 ml acetone andfiltered to remove sodium chloride. The acetone filtrate is nextevaporated to dryness to give essentially pure carboxymethyloxysuccinicacid as a residue.

The carboxymethyloxysuccinic acid from above is mixed with 100 mls ofacetyl chloride in a reaction flask equipped with a condenser. Theresulting mixture refluxed until all of the acid is dissolved and theevolution of hydrogen chloride has essentially ceased. The reactionmixture is then evaporated in vacuo to form a syrupy residue. The syrupresidue is mixed with about 100 mls of methylene chloride and theresulting solution heated while acetone is gradually added until acomplete solution occurs. The resulting solution is then cooled to -70°C. (dry ice/acetone bath) and the solid which crystallizes out isimmediately filtered by suction and placed in a vacuum dessicator. Thesolid, which liquifies at room temperature, is shown by infraredanalysis to consist of a mixture of five-membered (5.36 μ) andsix-membered anhydride (5.8 μ) species together with linear anhydridepolymers.

EXAMPLE 2 Preparation of Carboxymethyloxysuccinic MonoAnhydride--Formula II

A. Ten grams of carboxymethyloxysuccinic acid (95.5% pure; 3% moisture),0.2 g of p-toluenesulfonic acid monohydrate and 300 mls of xylene areplaced in a 500 ml flask equipped with a condenser and Dean Starkapparatus. The mixture is then refluxed for three hours during whichtime 1 ml water separates in the water separator. The xylene layer isdecanted and the remaining syrupy residue is taken up in 150 ml ofacetone. The acetone is evaporated to a syrupy residue which is thenplaced in a vacuum oven at 90° C. to remove residual traces of solvents.The product, 8 g, is shown by infrared analysis to consist of a mixturecontaining predominantly five-membered anhydride species containing freecarboxyl groups.

B. To 10 g (0.05 mole) of 95.5% CMOSA dissolved in 17 g of dioxane isadded 8 g (0.067 mole) of thionyl chloride. The solution is thenrefluxed for forty minutes. The solution is then evaporated in vacuo toremove solvent and any excess thionyl chloride. A liquid residue of 9.4g containing predominantly the desired product of Formula II wasobtained. Infrared analysis confirmed the presence of a five-memberedanhydride moiety (5.35 μ) and the characteristic band for COOHstretching (2.8-4.4 μ).

EXAMPLE 3 Preparation of Monomethyl Dihydrogen Carboxymethyloxysuccinate

Two grams of Formula II species prepared as described in Example 2 isdissolved in 10 ml of methanol by heating to reflux. The methanolicsolution is then evaporated in vacuo to give a liquid residue of amixture of monomethyl esters of carboxymethyloxysuccinic acid. NMRanalysis shows the presence of three distinct types of methyl estergroups (3.74δ, 3.80δ and 3.81δ) corresponding to the three differenttypes of carboxyl groups possible in carboxymethyloxysuccinic acid.

The presence of the three types of ester groups instead of the expectedtwo is believed to be due to a randomization of the methyl groups amongall the possible carboxyl groups during the reaction and work up.

EXAMPLE 4 Preparation of Chlorocarbonylmethyloxysuccinic anhydride -(Formula III, A=Cl)

Carboxymethyloxysuccinic acid, 18.8 g (95.5% purity; 0.094 mole) ismixed with 48 g (0.41 mole) thionyl chloride and 100 mls of chloroform.The resulting mixture is refluxed for three hours thereby producing alight yellow reaction solution. The reaction solution is evaporated invacuo to give 17.2 g of the desired compound. NMR and infrared analysisof the compound are consistent with predominantly a five-memberedanhydride ring and acid chloride function:

    ______________________________________                                         ##STR18##                                                                    NMR (CDCl.sub.3):                                                                       CH.sub.2 (a) ABX multiplet at 2.80-3.80δ                                CH(b) ABX multiplet at 4.60-5.00δ                                       CH.sub.2 (c) singlet at 4.89δ                                 Infrared:                                                                               5-membered anhydride carbonyl, 5.35δ                                    acid chloride (COCl) carbonyl, 5.56δ                                    OH-stretching band for COOH is absent                               ______________________________________                                    

EXAMPLE 5 Preparation of Dimethyl Hydrogen Carboxymethyloxysuccinates

One gram of the mixed anhydride acid chloride ofcarboxymethyloxysuccinic acid prepared as described in Example 4 isdissolved in 10 mls of methanol. The solution is then evaporated and theresidue warmed gently in vacuo to remove the last traces of methanol.NMR (DCl₃) analysis of the residue is consistent with a mixture of thefollowing dimethyl esters of carboxymethyloxysuccinic acid: ##STR19##

EXAMPLE 6 Preparation of Carboxymethyloxysuccinic Trichloride (FormulaIV, A=Cl)

Thionyl chloride, 23 g (0.17 mole), is added to a mixture of 5 g of95.5% (0.025 mole) carboxymethyloxysuccinic acid and 0.5 g of anhydrouszinc chloride. The resulting mixture is stirred at 25° C. until theCMOSA dissolves (about 2 hours). The clear reaction solution is decantedinto a clear flask and the excess thionyl chloride is distilled off invacuo (water pump). The residue, 4 g, is identified as the desiredproduct by NMR (CDCl₃): ##STR20##

EXAMPLE 7 Preparation of Trimethyl Carboxymethyloxysuccinate

One-half gram of carboxymethyloxysuccinic trichloride prepared asdescribed in Example 6 is dissolved in 5 ml methanol, heated for a fewminutes and then the excess methanol is distilled off in vacuo (waterpump). The NMR (CDCl₃) spectrum of the residue is identical to that ofauthentic trimethyl carboxymethyloxysuccinate prepared by esterificationof CMOSA with methanol according to the method of U.S. Pat. No.3,943,165. ##STR21##

Modifications will occur to those skilled in the art in view of theforegoing description and such modifications are to be included withinthe purview of the invention.

What is claimed is:
 1. Carboxymethyloxysuccinic trihalides of theformula: ##STR22## wherein A is Cl, Br or I.
 2. The compound of claim 1wherein A is Cl.